The aims of this project are oriented onthe use of immunochemical methods, and particularly the radioimmunoassay(RIA) developed in my laboratory, to detect, quantify, and elucidate the role of the metal-binding protein, metallothionein(MT), in fluids and tissues of humans exposed to toxic metals sequestered by MT, particularly Cadmium(Cd) but including Copper(Cu), Mercury(Hg), Platinum(Pt), Gold(Au) and the normally non-toxic Zinc(Zn). The aims include the following: (1) Determination of the role of MT in toxicities in workers exposed to Cd. Three such studies are in progress, all long-term (3-5 years). Samples of sera and urines from Cd. Three such studies are in progress, all long-term (3-5 years). Samples of sera and urines from Cd-exposed workers in Belgium, Sweden, and this country are analyzed for MT and Cd content and for other physiological variables to correlate with MT and Cd. The goal is the development of a sound data base to permit the expression of a definitive theory of MT, Cd(and Zn) metabolism in the body. In conjunction with aims (2) and (3) below, this theory can be extended to include all toxic metals of interest. (2) Determination of the role of TM in pathological states associated with toxic metals and disturbed MT-metal metabolism. Studies in progress include analysis of MT and metal content inbody fluids of patients with Wilson's disease (excess Cuconcentrations), inplacental tissues in cases of disorders associated with excess Cd concentration and maternal smoking, and in body fluids of infants with nervous system defects associated with faulty Zn metabolism. (3) Determination of the role of MT in toxicities associated with the use of Au compounds in treatment of rheumatoid arthritis and with Pt compounds in treatment of genito-urinary cancers. This study involves analysis of various Au-MTs and of MTs produced by compounds such as cis-platin and trans-platin. The long-term aim of (2) and (3) is the development of improved treatment protocols as well as improved theories of MT-metal metabolism. (4) Development of immunochemical methods to supplement the RIA, including the ElISA as an alternative method and monoclonal antibodies to permit identification of MT isoforms and to better define MT antigenicity and tertiary structure. (5) Continued action as a service center for scientists requesting analysis of various MTs and candidate MTs. In pursuit of the above aims, my laboratory and others available to me have capabilities in all analytical methods complementary to the immunochemical methods and requisite to achieve the stated aims.